ABSTRACT This renewal proposes three main goals in our studies of aging among Tsimane. This forager-horticultural society presents a unique and fleeting opportunity to study health transitions from a pre-modern context during the acculturation that is increasing their lifespan. We will: I) Further document with longitudinal data the details of aging with biomarkers, functional changes and disease burden. II) Test the hypothesis that aging among the Tsimane is accelerated relative to people in developed nations due to the heavy burden of infectious disease and low energy balance. III) Evaluate "embodied capital" theory of human life history and aging developed by the PIs during the course of their research program. These goals are addressed by four specific aims: Aim 1, Characterize immunosenescence;Aim 2, Determine prevalence of arterial, heart and kidney disease, and associated etiology;Aim 3, Obtain longitudinal sampling of morbidity, co-morbidity, mortality, physical and cognitive function, energy production, and social roles after age 45;Aim 4, Examine age- and sex-related changes in sex and metabolic hormones and their relationship to health and energy supply. We propose to build a longitudinal profile of a large sample of Tsimane across the lifespan into oldest ages in a population that reached maturity in a pre-modern, highly infectious environment and is only now beginning to experience an epidemiological transition. We will analyze how physical and cognitive functioning are altered by infection, nutrition, organ function and damage. Each aim will compare Tsimane to U.S. and other modern populations. We will also assess the effects of the within-population variance in acculturation at both the community and individual levels on those outcome variables. In so doing, we will model the effects of changing economic activities, housing conditions, use of medical facilities, Spanish competency, and literacy, and link them to data on health, physical and cognitive status, and mortality. The intra-population gradients of infection and life expectancy or mortality will provide further basis for evolutionary hypotheses about relationships between infection, inflammation and the pathophysiology of aging.